ArticleScience translational medicine2015
Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03893344 (Detection of STAT4 in Multiple Sclerotic Patients by Polymerase Chain Reaction and Flow Cytometry), which is not on this map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Detection of STAT4 in Multiple Sclerotic Patients by Polymerase Chain Reaction and Flow Cytometry
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
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- The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto's Thyroiditis.Frontiers in immunology · 2018Trial
- Multiple sclerosis and autoimmunity: a reappraisal of the evidence.Frontiers in immunology · 2026Review
- Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways.medRxiv : the preprint server for health sciences · 2025Article
- Genetic variants associated with gout identified through a genome-wide study in the UK biobank (N = 150 542).Human molecular genetics · 2025Article
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- Common genetic factors among autoimmune diseases.Science (New York, N.Y.) · 2023Review
- Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.Journal of translational medicine · 2023Article
- Genetics and functional genomics of multiple sclerosis.Seminars in immunopathology · 2022Review
- Bcl-3 regulates the function of Th17 cells through raptor mediated glycolysis metabolism.Frontiers in immunology · 2022Article
- Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation.Frontiers in immunology · 2022Review
- The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis.Genome medicine · 2021Article
- Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences.Biomedicines · 2020Review
- Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis.CNS neuroscience & therapeutics · 2020Article
- Review
- Failed, Interrupted, or Inconclusive Trials on Immunomodulatory Treatment Strategies in Multiple Sclerosis: Update 2015-2020.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features.Nature communications · 2020Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
The transcription factor nuclear factor κB (NFκB) is a central regulator of inflammation, and genome-wide association studies in subjects with autoimmune disease have identified a number of variants within the NFκB signaling cascade. In addition, causal variant fine-mapping has demonstrated that autoimmune disease susceptibility variants for multiple sclerosis (MS) and ulcerative colitis are strongly enriched within binding sites for NFκB. We report that MS-associated variants proximal to NFκB1 and in an intron of TNFRSF1A (TNFR1) are associated with increased NFκB signaling after tumor necrosis factor-α (TNFα) stimulation. Both variants result in increased degradation of inhibitor of NFκB α (IκBα), a negative regulator of NFκB, and nuclear translocation of p65 NFκB. The variant proximal to NFκB1 controls signaling responses by altering the expression of NFκB itself, with the GG risk genotype expressing 20-fold more p50 NFκB and diminished expression of the negative regulators of the NFκB pathway: TNFα-induced protein 3 (TNFAIP3), B cell leukemia 3 (BCL3), and cellular inhibitor of apoptosis 1 (CIAP1). Finally, naïve CD4 T cells from patients with MS express enhanced activation of p65 NFκB. These results demonstrate that genetic variants associated with risk of developing MS alter NFκB signaling pathways, resulting in enhanced NFκB activation and greater responsiveness to inflammatory stimuli. As such, this suggests that rapid genetic screening for variants associated with NFκB signaling may identify individuals amenable to NFκB or cytokine blockade.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.